A commercially viable vaccine for the prevention of West Nile virus infection is the overall objective of this project. West Nile virus was isolated for the first time in the Western hemisphere in 1999, when seven New York patients died as a result of a West Nile virus outbreak. The virus is still present in North America. A vaccine will be an important complement to other public health measures, particularly if this emerging pathogen becomes endemic in North America. Phase I of the project will study immunogens based on the envelope protein of a U.S. West Nile virus isolate. To date, we have prepared recombinant protein and synthetic peptide antigens, and have initiated preliminary immunization studies. In Phase I, mice will be vaccinated with these antigens, antibody responses will be evaluated, and protective immunity investigated. The antigens may also be suitable for serodiagnostic tests. Phase II experiments will further develop vaccine candidates, and include demonstration of efficacy in a murine model of mosquito- transmitted infection. This project will provide clinicians and public health officials with important means of managing outbreaks of West Nile virus. PROPOSED COMMERCIAL APPLICATIONS: Our primary goal is to commercialize a West Nile Virus vaccine to protect against potentially fatal West Nile virus infection. It may take 3 to 5 years for the virus establish itself in North American wetland and urban ecosystems, putting significant numbers of U.S. citizens at risk. It is important to initiate vaccine development now, so that we are prepared for future outbreaks of the virus. A potential commercial by- product of the proposed research is a serodiagnostic ELISA to aid physicians in evaluating suspected cases of West Nile virus infection. Commercial opportunities for veterinary vaccines also exist.